Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads toa functionally heterogeneous CTL response

The goal of experimental clinical protocols using peptide antigen for activ e vaccination and treatment of patients with metastatic cancer is to induce a vigorous cytotoxic T lymphocyte (CTL) response against the immunizing an tigen, and thereby against tumor cells expressing the antigen. However, the magnitude and breadth of human CTL responses induced by peptide immunizati on, and in particular against antigens expressed by normal tissues as well as tumors, is not well characterized. This issue was examined by characteri zing CTL cloids derived from peripheral blood mononuclear cells of three pa tients who received peptide immunization as treatment for metastatic melano ma. All patients received G9-209-2M peptide, a modified epitope of the gp10 0 melanoma-associated antigen. The results indicated that the CTL response induced by this peptide antigen was highly heterogeneous both in terms of a vidity toward the peptide antigen and recognition of tumor cell lines. Furt hermore, avidity of each CTL cloid for the native peptide was highly predic tive of tumor reactivity. These results are discussed in terms of their imp lications for peptide vaccination and adoptive tumor immunotherapy.